Understanding how tissue disorganisation leads to breast cancer

Loss of the proper orientation of cells within a tissue, known as cell polarity, is one of the hallmarks of breast cancer and is correlated with more aggressive and invasive cancers. However how loss of cell polarity occurs and how it contributes at the molecular level to tumour formation remains unknown. Using a number of approaches including RNAi screening, our laboratory has identified a network of genes that mediate the tumour suppressive functions of cell polarity. We aim to use this new molecular information to re-establish normal tissue architecture and hence stop tumour growth.

This project characterizes the top key novel candidates and nodes from this gene network using a variety of biochemical, cell biological and functional assays set up in our laboratory. These include gene knockdown studies in 3D mammary organoid cultures, analysis of genetically engineered mouse models of breast cancer, and mammary gland reconstitution experiments involving the surgical transplantation of RNAi modified mammary stem cells into host mice. In addition, there is also an opportunity to use the powerful genetics of cancer models in Drosophila to complement these studies. The above experiments will provide essential information as to the requirement for intact polarity signaling in breast cancer development and the molecular pathways regulated by the genes that control tissue organization to suppress invasion and tumour growth.